Department of Orthopedics, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Hematology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China.
Mol Cancer Ther. 2020 Feb;19(2):650-660. doi: 10.1158/1535-7163.MCT-18-0783. Epub 2019 Nov 6.
Bone metastasis is a severe complication associated with various carcinomas. It causes debilitating pain and pathologic fractures and dramatically impairs patients' quality of life. Drugs aimed at osteoclast formation significantly reduce the incidence of skeletal complications and are currently the standard treatment for patients with bone metastases. Here, we reported that serum- and glucocorticoid-inducible kinase 1 (SGK1) plays a pivotal role in the formation and function of osteoclasts by regulating the Ca release-activated Ca channel Orai1. We showed that SGK1 inhibition represses osteoclastogenesis and prevents bone loss Furthermore, we validated the effect of SGK1 on bone metastasis by using an intracardiac injection model in mice. Inhibition of SGK1 resulted in a significant reduction in bone metastasis. Subsequently, the Oncomine and the OncoLnc database were employed to verify the differential expression and the association with clinical outcome of gene in patients with breast cancer. Our data mechanistically demonstrated the regulation of the SGK1 in the process of osteoclastogenesis and revealed SGK1 as a valuable target for curing bone metastasis diseases.
骨转移是与多种癌症相关的严重并发症。它会导致虚弱性疼痛和病理性骨折，并极大地降低患者的生活质量。针对破骨细胞形成的药物可显著降低骨骼并发症的发生率，目前是治疗骨转移患者的标准治疗方法。在这里，我们报道了血清和糖皮质激素诱导的激酶 1（SGK1）通过调节钙释放激活钙通道 Orai1 在破骨细胞的形成和功能中发挥关键作用。我们表明，SGK1 抑制可抑制破骨细胞生成 并防止骨质流失 此外，我们通过在小鼠中心内注射模型验证了 SGK1 对骨转移的影响。SGK1 的抑制导致骨转移显著减少。随后，使用 Oncomine 和 OncoLnc 数据库验证了基因在乳腺癌患者中的差异表达及其与临床结局的关联。我们的数据从机制上证明了 SGK1 在破骨细胞生成过程中的调节作用，并揭示了 SGK1 是治疗骨转移疾病的有价值的靶点。
